title: Tetrahydrobiopterin therapy vs phenylalanine-restricted diet: impact on growth in PKU.
abstract: BACKGROUND
  Treatment of phenylketonuria based upon strict vegetarian diets, with very low phenylalanine intake and supplemented by phenylalanine-free formula, has proven to be effective in preventing the development of long-term neurological sequelae due to phenylalanine accumulation. On the other hand, such diets have occasionally been reported to hinder normal development, some individuals presenting with growth retardation. Tetrahydrobiopterin therapy has opened up new treatment options for a significant proportion of phenylketonuric patients, enabling them to eat normal diets and be freed from the need to take synthetic supplements. However, little is known about how this therapy affects their physical development.
  
  
  METHODS
  We conducted a retrospective longitudinal study examining anthropometric characteristics (height, weight, body mass index and growth speed Z-scores) in a cohort of phenylketonuric patients on tetrahydrobiopterin therapy (38 subjects) comparing their characteristics with those of a group of phenylketonuric patients on phenylalanine-restricted diets (76 subjects). Nutritional issues were also considered, to further explore the possibility of higher natural protein intake being associated with better physical development. Data were collected every six months over two different periods of time (two or five years).
  
  
  RESULTS
  No improvement was observed in the aforementioned anthropometric variables in the cohort on tetrahydrobiopterin therapy, from prior to starting treatment to when they had been taking the drug for two or five years. Rather, in almost all cases there was a fall in the mean Z-score for the variables during these periods, although the changes were not significant in any case. Further, we found no statistically differences between the two groups at any considered time point. Growth impairment was also noted in the phenylketonuric patients on low-phenylalanine diets. Individuals on tetrahydrobiopterin therapy increased their natural protein intake and, in some instances, this treatment enabled individuals to eat normal diets, with protein intake meeting RDAs. No association was found, however, between higher protein intake and growth.
  
  
  CONCLUSIONS
  Our study identified growth impairment in patients with phenylketonuria on tetrahydrobiopterin, despite higher intakes of natural proteins. In fact, individuals undergoing long-term tetrahydrobiopterin treatment seemed to achieve similar developmental outcomes to those attained by individuals on more restricted diets.
authors.affiliation: Division of Metabolism, Cruces University Hospital, Plaza de Cruces, s/n, 48903 Barakaldo, Spain. luisjose.aldamiz-echevarazuara@osakidetza.net
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
authors.forename: María A
authors.initials: MA
authors.lastname: Bueno
authors.forename: María L
authors.initials: ML
authors.lastname: Couce
authors.forename: Sergio
authors.initials: S
authors.lastname: Lage
authors.forename: Jaime
authors.initials: J
authors.lastname: Dalmau
authors.forename: Isidro
authors.initials: I
authors.lastname: Vitoria
authors.forename: Fernando
authors.initials: F
authors.lastname: Andrade
authors.forename: Marta
authors.initials: M
authors.lastname: Llarena
authors.forename: Javier
authors.initials: J
authors.lastname: Blasco
authors.forename: Carlos
authors.initials: C
authors.lastname: Alcalde
authors.forename: David
authors.initials: D
authors.lastname: Gil
authors.forename: María C
authors.initials: MC
authors.lastname: García
authors.forename: Domingo
authors.initials: D
authors.lastname: González-Lamuño
authors.forename: Mónica
authors.initials: M
authors.lastname: Ruiz
authors.forename: María A
authors.initials: MA
authors.lastname: Ruiz
authors.forename: David
authors.initials: D
authors.lastname: González
authors.forename: Felix
authors.initials: F
authors.lastname: Sánchez-Valverde
mesh_terms: D001708:Biopterins / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001823:Body Composition / Q000187:drug effects; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D005500:Follow-Up Studies; D006801:Humans; D010649:Phenylalanine / Q000008:administration & dosage / Q000378:metabolism*; D010661:Phenylketonurias / Q000178:diet therapy* / Q000473:pathology
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin
keywords: Growth; Phenylketonuria; Tetrahydrobiopterin